Prostate cancer (PCa) is one of the most common cancers worldwide and the most common cancer in men. However, treatment strategies remain highly controversial. Radical prostatectomy (RP), or complete removal of the prostate gland, is a common treatment option for men with early-stage PCa. Long-term data indicate that 30-40% of these patients experience rising prostate-specific antigen (PSA) levels after RP, indicating continued survival of prostate cells. A significant rise in PSA level after RP may be termed a “biochemical failure” (BF), “biochemical recurrence”, or “biochemical relapse”. At this point, a patient may opt for salvage radiation therapy (RT), adjuvant therapy, or both, depending on the prognosis from the clinician. For some patients, BF may occur again after the second round of therapy.
Currently, data used to develop prognoses after RP and RT include PSA levels, age, pathologic tumor (pT) and lymph node (pN) classification, and Gleason score. PSA is manufactured by cells of the prostate gland. A rising PSA level is considered a potential indicator of prostate cancer. Tumor stage (pT) indicates the size and invasiveness of the tumor (on a scale of 1-4, 1 being smallest and least invasive). The lymph node score (pN) indicates whether or not the cancer has spread to the lymph nodes near the prostate gland. This value is either a 0 if the cancer is not present in the lymph nodes, or a 1 if the cancer is found in the lymph nodes.
The Gleason score takes into account the ability of the tumor to form glands (an indication of healthier tissue). A pathologist assigns a primary grade based on the most prominent tissue seen in the tumor, and a secondary grade based on the second most prominent or the most aggressive types of tissue seen in the tumor. The range of grades is 1-5: 1, 2 and 3 are considered to be low to moderate in grade (many smaller, more uniform glands); 4 and 5 are considered to be high grade (few glands). The prognosis for a given patient generally falls somewhere between that predicted by the primary grade and a secondary grade given to the second most prominent glandular pattern. When the two grades are added the resulting number is referred to as the Gleason score. The Gleason Score is a more accurate predictor of outcome than either of the individual grades. Thus, the traditionally reported Gleason score will be the sum of two numbers between 1-5 with a total score from 2-10.
Multiple risk assessment nomograms and classification models have been derived utilizing parameters such as the pT, pN, Gleason score, or resection status. These models include the CAPRA score, Partin table, D'Amico classification, and the three Stephenson Nomograms. However, it is still difficult to distinguish between aggressive and indolent prostate cancers. The lack of clear predictors of prostate cancer progression leads to subjective decision-making regarding courses of treatment. Some prostate tumors grow so slowly that they never cause life threatening problems, making early-stage treatment controversial. Therefore, biomarkers that predict the progression of PCa are needed to guide therapy.